2-Decarboxy-2-alkylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-PGF1 compounds

ABSTRACT

The present invention provides novel prostaglandin analogs wherein the C-2 carboxyl is replaced by alkylcarbonyl, i.e., a C-2 ketone. These novel 2-decarboxy-2-alkylcarbonyl-PG-type compounds are disclosed as improved gastrointestinal cytoprotective agents, being devoid or substantially devoid of other prostaglandin-type effects (e.g., smooth muscle or cardiovascular).

The present application is a divisional application of Ser. No. 888,695,filed Mar. 21, 1978, now U.S. Pat. No. 4,123,463.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. U.S. Pat. No. 4,123,463.

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is##STR2## wherein R₁ is alkyl of one to 4 carbon atoms, inclusive;wherein L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ arehydrogen, methyl, or fluoro, being the same or different, with theproviso that one of R₃ and R₄ is methyl only when the other is hydrogenor methyl;wherein M₁ is ##STR5## wherein R₅ is hydrogen or methyl;wherein R₇ is (1) --(CH₂)_(m) --CH₃ --, ##STR6## wherein h is zero tothree, inclusive, wherein m is one to 5, inclusive, s is zero, one, 2,or 3 and T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbonatoms or alkoxy of one to 3 carbon atoms, the various T's being the sameor different, with the proviso that not more than two T's are other thanalkyl; wherein Y₁ is (1) trans--CH═CH--, (2) cis--CH═CH--, (3) --CH₂ CH₂--, or (4) --C.tbd.C--; and wherein Z₁ is ##STR7## wherein g is one,two, or three.
 2. A prostaglandin analog according to claim 1, whereinR₁ is methyl.
 3. A prostaglandin analog according to claim 2, wherein Dis ##STR8## 4.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-8.beta.,12α-PGF₁α, a prostaglandin analog according to claim
 3. 5. A prostaglandinanalog according to claim 2, wherein D is ##STR9## 6.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-PGF₁β, a prostaglandin analog accoridng to claim
 5. 7. A prostaglandinanalog according to claim 5, wherein D is ##STR10## 8.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-8.beta.,12α-PGF₂ β, a prostaglandin analog according to claim
 7. 9. Aprostaglandin analog according to claim 2, wherein D is ##STR11## 10.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-PGE₁,a prostaglandin analog according to claim
 9. 11. A protaglandin analogaccording to claim 2, wherein D is ##STR12## 12.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-8.beta.,12α-PGE₁, a prostaglandin analog according to claim
 11. 13. Aprostaglandin analog according to claim 2, wherein D is ##STR13##
 14. Aprostaglandin analog according to claim 13, wherein Y₁ is cis--CH═CH--.15.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-13-cis-PGF₁α, a prostaglandin analog according to claim
 14. 16. A prostaglandinanalog according to claim 13, wherein Y₁ is --CH₂ CH₂ --. 17.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-13,14-dihydroPGF₁ α, a prostaglandin analog according to claim
 16. 18. Aprostaglandin analog according to claim 13, wherein Y₁ is --C.tbd.C--.19.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-13,14-didehydro-PGF₁α, a prostaglandin analog according to claim
 18. 20. A prostaglandinanalog according to claim 13, wherein Y₁ is trans--CH═CH--.
 21. Aprostaglandin analog according to claim 20, wherein R₇ is ##STR14## 22.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-18,19,20-hexanor-17-phenyl-PGF₁α, a prostaglandin analog according to claim
 21. 23. prostaglandinanalog according to claim 20, wherein R₇ is ##STR15## 24.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-17,18,19,20-heptanor-16-phenoxy-PGF₁α, a prostaglandin analog according to claim
 23. 25. A prostaglandinanalog according to claim 20, wherein R₇ is --(CH₂)_(m) --CH₃ --.
 26. Aprostaglandin analog according to claim 25, wherein Z₁ is ##STR16## 27.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-4,5,6-trinor-PGF.sub.1α, a prostaglandin analog according to claim
 26. 28. A prostaglandinanalog according to claim 25, wherein Z₁ is ##STR17##
 29. Aprostaglandin analog according to claim 25, wherein R₅ is methyl. 30.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-15-methyl-PGF₁α, a prostaglandin analog according to claim
 25. 31. A prostaglandinanalog according to claim 25, wherein R₅ is hydrogen.
 32. Aprostaglandin analog according to claim 31, wherein one of R₃ and R₄ isfluoro. 33.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-16,16-difluoro-PGF₁α, a prostaglandin analog according to claim
 32. 34. A prostaglandinanalog according to claim 31, wherein at least one of R₃ and R₄ ismethyl. 35.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-16,16-dimethyl-PGF₁α, a prostaglandin analog according to claim
 34. 36. A prostaglandinanalog according to claim 31, wherein R₃ and R₄ are both hydrogen. 37.2-Decarboxy-2-methylcarbonyl-3,7-inter-m-phenylene-3-oxa-4,5,6-trinor-PGF₁α, a prostaglandin analog according to claim 36.